論文No1897

Validation of the immunohistochemical expression of programmed death ligand 1 (PD-L1) on cytological smears in advanced non small cell lung cancer

Elisa Capizzi, Costantino Ricci, Francesca Giunchi, Stefano Zagnoni, Claudio Ceccarelli, Begoña Urrios Álvarez Gómez, Laura Casolari, Francesco Gelsomino, Rocco Trisolini, Michelangelo Fiorentino, Andrea Ardizzoni

Lung Cancer, Volume 126, p9–14, 2018.

＜背景＞

免疫組織化学によるPD-L1発現の評価は進行NSCLC患者に対する

抗PD-1阻害薬であるペムブロリズマブの1st line治療導入に必須である。

現在、ホルマリン固定パラフィン包埋のサンプルのみが

PD-L1の免疫染色（抗PD-L1抗体22-C3およびSP263）に適している。

我々はNSCLC患者の組織学的サンプルと細胞診スメアとで22-C3、28-28、SP263の正確性について後ろ向きに検討した。

＜結果＞

組織学的サンプルにおけるPD-L1の検出の正確性はSP263(AUC/ROC = 1)が

28-28(AUC/ROC =,991)、22-C3 (AUC/ROC =,942)よりも高かった。

組織学的サンプルと細胞診スメアのSP263に対する全体の一致率は中等度(kappa = 0,364)であった。

しかし、細胞診と組織診で<50% vs ≧50%のカットオフの一致率はよかった(kappa = 0.626)。

細胞診スメアのSP263抗体の成果性は良好であった(AUC/ROC =,921)。

蛍光染色のin situ hybridizationをPD-L1陽性の組織化学的に行ったところ、CD274遺伝子増幅を１例のみに認めた。

＜感想＞

>50%のがん細胞のスメアでは細胞診のスメアのPD-L1染色はまずまずだったようです。

細胞診ではSP263がPD-L1染色として最もよかったようです。

Introduction The assessment of PD-L1 expression by immunohistochemistry is mandatory for the administration as first-line therapy of the anti PD-1 check-point inhibitor Pembrolizumab in patients with advanced non-small-cell lung cancer (NSCLC). Currently, only formalin-fixed paraffin-embedded samples are acceptable for PD-L1 immunostaining with the anti-PD-L1 antibodies 22-C3 and SP263. We investigated retrospectively the accuracy of the anti PD-L1 antibodies 22-C3, 28-28, SP263 in 50 paired histological samples and cytological smears of NSCLC patients.

Results The accuracy of the three antibodies for the detection of PD-L1 in histological samples was higher for the antibody SP263 (AUC/ROC = 1) compared to the clones 28-8 (AUC/ROC =,991) and 22-C3 (AUC/ROC =,942). The overall concordance between histological samples and cytological smears using the SP263 clone was moderate (kappa = 0,364). However when the cyto-histological concordance was calculated using just the <50% vs ≥50% cut-off the agreement (kappa = 0.626) was good. The accuracy of the antibody SP263 in cytological smears was good (AUC/ROC =,921). A fluorescent in situ hybridization analysis on 10 histological cases positive for PD-L1 at immunohistochemistry showed amplification of the CD274 gene only in one case.

Conclusions Immunocytochemical staining for PD-L1 in diagnostic cytological smears of NSCLC is feasible and applicable at least using the >50% cancer cell cut-off. The three antibodies SP263, 22-C3 and 28-8 are all suitable for the diagnostic detection of PD-L1 on tissue sections with a superiority of the SP263 clone. The implementation of PD-L1 immunocytochemistry on cytological smears will likely expand the pool of NSCLC patients candidate to first-line immunotherapy.